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55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

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Glioma with acquired resistance to temozolomide are characterized by an increased tumour angiogenic activity and improved tumour perfusion

Temozolomide-resistente Gliome sind durch eine erhöhte Tumorangiogenese und verbesserte Tumorperfusion charakterisiert

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  • corresponding author Tobias Korn - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Mannheim
  • R. Erber - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Mannheim
  • V. Powajbo - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Mannheim
  • J. Gallo - Department of Pharmacology, Fox Chase Cancer Center, Philadelphia /USA
  • P. Vajkoczy - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Mannheim

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocMO.04.05

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2004/04dgnc0048.shtml

Published: April 23, 2004

© 2004 Korn et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective

The anti-glioma efficacy of temozolomide (TMZ) is hampered by the rapid development of tumour cell resistance to TMZ. For these tumours with acquired resistance to chemotherapy, anti-angiogenesis has been suggested as a treatment alternative targeting the vascular instead of the tumour cell compartment. This paradigm, however, affords adequate tumour perfusion, vascular drug delivery and angiogenic activity of resistant tumours, none of which has been addressed so far. Therefore, the aim of the present study was to characterize the vascular compartment of TMZ-resistant versus TMZ-sensitive tumours.

Methods

The TMZ-sensitive human glioma cell line SF188 was exposed continuously to increasing concentrations of TMZ (from 50 to 300 μg/ml) over a 6-month period in order to generate the TMZ-resistant cell clone SF188/TR. Both cell lines were implanted into dorsal skinfold chamber preparations of nude mice and tumour angiogenesis, perfusion and angioarchitecture were assessed by intravital multi-fluorescence videomicroscopy over 21 days. The angiogenic expression profile of cell lines and xenografts was assessed on the mRNA and protein level.

Results

SF188/TR cells were characterized by an increased tumour angiogenic activity as indicated by their significantly higher total vessel density when compared to SF188 cells. Furthermore, SF188/TR tumours were characterized by a significantly higher functional vessel density and comparable vessel diameters, in combination resulting in an improved tumour perfusion. Angiogenic expression profiling revealed a significant increase in cyclooxygenase-2 expression in the SF188/TR cells and xenografts.

Conclusions

Our results suggest that the development of TMZ-resistance has a significant impact not only on the tumour cell but also on the vascular compartment of glioma. Based on an increased angiogenic activity TMZ-resistant glioma may represent a suitable target for anti-angiogenesis.